Lactate Concentration Research Articles

Effects of lactic acid etching on immediate and aged bond strength of resin-dentin bonding interface.

To investigate the effects of lactic acid etching on the immediate and aged bond strength of the resin-dentin bonding interface, the resin-dentin bonding interface was evaluated 24 hours and 6 months later. A total of 42 isolated third molars were randomly divided into 6 experimental groups according to different lactate concentration (35%, 40%, 45%) and acid etching time (30 s, 45 s), with 37% phosphoric acid etching 15 s as a control. In each group, dentin samples were etched under different acidic conditions and bonded with Adper Single Bond 2 (3M ESPE) as directed. The immediate group was immediately stored in deionized water at 37 °C for 24 h, and the aging group was stored in artificial saliva at 37 °C for 6 months. Immediate and aged bond strengths were measured by a micro-tensile tester, and the specimen fracture surface was observed under a microscope. 14 isolated third molars were randomly divided into 7 groups, and each group was etched with acid. Collagen fibers morphology in dentin was examined after gradient dehydration with ethanol by scanning electron microscopy (SEM). Statistically, there was no difference between the resin-dentin immediate bonding strength of 35% lactic acid for 30 s and 37% phosphoric acid for 15 s, but the aged bond strength was greater than that of the phosphoric acid group. According to scanning electron microscope observations, the collagen fiber morphology in 35% and 40% lactate etching dentin 30 s groups was relatively intact compared with other groups. In conclusion, 35% lactic acid etching of dentin 30 s ensures both immediate and aged resin-dentin bond strength.

Lower or Higher Oxygenation Targets in Patients With COVID-19 in the ICU: A Secondary Bayesian Analysis of the Handling Oxygenation Targets in COVID-19 Trial

BackgroundIn the Handling Oxygenation Targets in COVID-19 (HOT-COVID) trial, a partial pressure of arterial oxygen (PaO2) target of 60 mmHg compared to 90 mmHg resulted in more days alive without life support at 90 days in adult ICU patients with coronavirus disease 2019 (COVID-19) and hypoxemia. The trial was stopped after enrolling 726 of 780 planned patients due to slow recruitment. Here, we present the preplanned Bayesian analysis of the HOT-COVID trial. Research QuestionWhat are the probabilities of any and of clinically relevant benefits from a PaO2 target of 60 mmHg versus 90 mmHg in adult ICU patients with COVID-19 and hypoxemia, and is there heterogeneity of treatment effects (HTE) according to selected baseline characteristics? Study Designand Methods We analyzed days alive without life support and 90-day mortality in the HOT-COVID intention-to-treat population (n=697) using Bayesian general linear models to assess probabilities for benefit or harm, including clinically relevant benefits defined as >1 day alive without life support and >2 percentage points lower 90-day mortality. HTE was evaluated based on baseline SOFA scores, PaO2:FiO2, norepinephrine doses, and lactate concentrations. ResultsThe mean difference in days alive without life support was 5.7 days (95% credible interval (CrI): 0.2 to 11.2), with a 95.2% probability of clinically relevant benefit and a 98.0% probability of any benefit from the lower PaO2 target. The risk difference in 90-day mortality was -4.6 percentage points (95% CrI: -11.8 to 2.6), with a 76.5% probability of a clinically relevant benefit from the lower target. HTE analyses revealed potential interaction with baseline norepinephrine dose and lactate concentrations for both outcomes. InterpretationIn ICU patients with COVID-19 and hypoxemia, we found high probability for a clinically relevant benefit of targeting a PaO2 of 60 mmHg vs. 90 mmHg on number of days alive without life support.

Myocardial oxygen handling and metabolic function of ex-situ perfused human hearts from circulatory death donors

BackgroundThis study investigated oxygen handling of human hearts donated after circulatory death (DCD) on normothermic ex-situ heart perfusion (ESHP) and evaluated oxygen handling markers as adjuncts to cardiac viability assessment. MethodsThis single-center retrospective study included human DCD heart transplantation procedures using ESHP. Lactate concentrations, blood gas, myocardial oxygen consumption (MVO2), delivery (MDO2) and extraction (MEO2), coronary blood flow (CBF), coronary vascular resistance (CVR), and adenosine infusion were reported over time. Correlation between parameters was assessed, and statistical testing compared patients who did and did not require extracorporeal membrane oxygenation (ECMO) support after transplantation. ResultsLactate concentrations decreased during ESHP in all transplanted hearts (n=25) and increased in 1 rejected heart. Arterial PO2 was 75.2±2.9 kPa, with an arteriovenous ΔPO2 of 44.8±10.4 kPa. Oxygen saturation was 100% in most arterial and venous samples. Average MVO2 was 2.7±0.6 mL·min-1·100·g-1 myocardium, MDO2 98.5±20.4 mL·min-1, and MEO2 8.6±1.8%. Average CVR was 0.025±0.006 mmHg∙min∙mL-1∙100 g-1 and increased over time. ΔPO2 correlated strongly with MVO2 (R=0.797, p<0.001) and lactate trend (R=0.799, p<0.001) in transplanted hearts, without differences compared to the rejected heart with increasing lactate. Adenosine infusion on ESHP was significantly higher in patients requiring ECMO post-transplantation versus non-ECMO cases (11.7 (4.5-21.0) vs. 2.2 (1.5-6.7) mL·h-1, p=0.039). ConclusionsHearts on normothermic ESHP receive excessive MDO2, due to high PO2 and CBF, while the MVO2 is relatively low. Thus, CBF and PO2 can potentially be lowered. Furthermore, ΔPO2 could serve as additional marker of metabolic function under these hyperoxic circumstances. The adenosine infusion rate might predict post-transplantation ECMO requirement.

Umbilical arterial blood lactate as predictor of early neonatal outcome and evaluation of intrapartum asphyxia

BackgroundPerinatal asphyxia is a leading cause of under-5 mortality and exerts great pressure on the health system. Adequate foetal monitoring in labour is paramount in the early detection of foetal distress to prevent perinatal asphyxia. Several methods of foetal monitoring are in use with varying efficacy. This study investigated the efficacy of umbilical arterial (UA) lactate assay in predicting adverse perinatal outcomes. MethodologyThis was a prospective longitudinal study involving 160 pregnant women in the active phase of labour at term who met the inclusion criteria. They were recruited using a consecutive sampling technique and underwent a cardiotocography. Then they were classified into normal and abnormal cardiotocographic groups. At delivery, the UA blood of all of the babies was collected and assayed for serum lactate, and the levels were correlated with the perinatal outcome. The perinatal outcomes were measured by Apgar scores, admission into the neonatal unit, and hypoxic ischaemic encephalopathy. Analysis was done to determine the sensitivity and specificity of UA lactate in predicting birth asphyxia, hypoxic ischaemic encephalopathy, and neonatal unit admission. ResultsThe mean age ± standard deviation (SD) between the two cardiotocography (CTG) groups, normal years (30.55 ± 5.59) and abnormal years (29.86 ± 5.51), were similar. A critical UA lactate concentration > 9.1 mmol/L predicted Apgar scores < 7 at 5 min with a sensitivity and specificity of 76.47% (CI: 50.1–93.2) and 91.55% (CI: 85.7–95.6%), respectively. Also, the need for neonatal unit admission was predicted at a cut-off point >9.1 mmol/L with a sensitivity of 61.90% (CI: 38.4–81.9) and specificity of 91.30% (CI: 85.3–95.4). Umbilical artery lactate levels > 11.2 mmol/L predicted the development of hypoxic ischaemic encephalopathy in neonates with a sensitivity of 100% (CI: 39.8–100.0) and specificity of 88.39% (CI: 82.3–93.0). ConclusionUmbilical artery lactate correlates with adverse pregnancy outcomes and is an excellent tool for predicting adverse neonatal outcome.

Moderately cool environment with rain and wind increases cold strain and energy expenditure via carbohydrate oxidation during running exercise.

Outdoor exercise often proceeds despite rain and wind in cool conditions. The aim of this study was to investigate the effects of rain with wind on physiological responses during running exercise at 70% V̇O<inf>2max</inf> in cool conditions. Eleven healthy men exercised on a treadmill at 70% V̇O<inf>2max</inf> intensity for 60 min under conditions of 10 mm/h rain and 3 m/sec wind (RW) or not (CON) at 10°C in a climatic chamber able to simulate various temperature, humidity, rain, and wind conditions. Body temperature, expired air, and blood samples were measured at rest and exercise. Rectal temperature, mean weighted skin temperature, and thermal sensation were all significantly lower in RW than in CON during exercise (all P<0.05). Oxygen uptake was significantly higher in RW than in CON during exercise (all P<0.05). Participants' rating of perceived exertion was significantly higher in RW than in CON at 50 and 60 min (P<0.05). Respiratory exchange ratio was significantly higher in RW than in CON at 10, 20, and 40 min. Plasma lactate concentration and plasma norepinephrine levels were significantly higher in RW than in CON during exercise (both P<0.05). Rain with wind intensified body heat loss, and energy expenditure and carbohydrate oxidation increased as the body cooled. These conditions may decrease exercise performance.

RNA-Seq Analysis of Glycolysis Regulation of Avian Leukosis Virus Subgroup J Replication.

Avian Leukosis virus (ALV) is a widely spread virus that causes major economic losses to the global poultry industry. This study aims to investigate the effect of glycolysis on the replication of the ALV-J virus and identify the key circular RNAs that regulate the replication of the ALV-J virus. We found that glucose uptake, pyruvate content, and lactate content in DF1 cells were increased after ALV-J infection. Moreover, inhibiting the glycolysis of ALV-J-infected DF1 cells reduced the replication of the ALV-J virus. To further study the mechanism of glycolysis in the replication of the ALV-J virus, we performed RNA-seq on ALV-J-infected and ALV-J-infected cells treated with glycolysis inhibition. RNA-seq results show that a total of 10,375 circular RNAs (circRNAs) were identified, of which the main types were exonic circular RNAs, and 28 circRNAs were differentially expressed between ALV-J-infected and ALV-J-infected cells treated with glycolysis inhibition. Then, we performed functional enrichment analysis of differentially expressed circRNA source and target genes. Functional enrichment analysis indicated that some circRNAs might be involved in regulating the replication of the ALV-J virus by influencing some pathways like glycolysis/gluconeogenesis, the NOD-like receptor signaling pathway, MAPK signaling pathway, p53 signaling pathway, Toll-like receptor signaling pathway, Insulin signaling pathway, and Apoptosis. This study revealed the effect of glycolysis on the replication of the ALV-J virus in DF1 cells and its possible regulatory mechanism, which provided a basis for understanding the factors influencing the replication of the ALV-J virus and reducing the rate of infection of the ALV-J virus in poultry.

Prehospital Lactate Levels Obtained in the Ambulance and Prediction of 2-Day In-Hospital Mortality in Patients With Traumatic Brain Injury.

To analyze the ability of prehospital lactate levels to predict 2-day in-hospital mortality in patients with traumatic brain injury (TBI), severe TBI (Glasgow Coma Scale (GCS) ≤ 8 points), and mild or moderate TBI (GCS ≥ 9 points). Second, 90-day mortality was also explored. This was a prospective, multicenter, emergency medical services (EMSs) delivery, ambulance-based, derivation-validation cohort study developed in 5 tertiary hospitals (Spain), from November 1, 2019, to July 31, 2022. Patients were recruited from among all phone requests for emergency assistance among adults who were later evacuated to referral hospitals with acute TBI. The exclusion criteria were minors, pregnancy, trauma patients without TBI, delayed presentations, patients were discharged in situ, participants with cardiac arrest, and unavailability to obtain a blood sample. The primary outcome was all-cause 2-day in-hospital mortality and 90-day mortality in patients with moderate or mild TBI compared with patients with severe TBI. Clinical and analytical parameters (lactate and glucose) were collected. The discriminative power (area under the receiver operating characteristic curve [AUC]) and calibration curve were calculated for 2 geographically separated cohorts. A total of 509 patients were ultimately included. The median age was 58 years (interquartile range: 43-75), and 167 patients were female (32.8%). The primary outcome occurred in 9 (2.2%) of 415 patients with moderate or mild TBI and in 42 (44.7%) of 94 patients with severe TBI. The predictive capacity of the lactate concentration was globally validated in our cohort, for which the AUC was 0.874 (95% CI 0.805-0.942) for the validation cohort. The ability of the GCS score to predict lactate concentration was greater in patients with a GCS score ≥9 points, with an AUC of 0.925 (95% CI 0.808-1.000) and a negative predictive value of 99.09 (95% CI 98.55-99.64) in the validation cohort. Our results show the benefit of using lactate in all patients with TBI, particularly in those with a GCS ≥9 points. Routine incorporation of lactate in the screening of patients with TBI could presumably reduce mortality and deterioration rates because of quicker and better identification of patients at risk.

Long-term hypoxia-induced physiological response in turbot Scophthalmus maximus L.

Hypoxia affects fish's survival, growth, and physiological metabolism processes. In this study, turbot plasma glucose and cortisol contents, hepatic glycolysis (hexokinase [HK], phosphofructokinase [PFK], pyruvate kinase [PK]) and lipolysis (fatty acid synthetase [FAS], lipoprotein lipase [LPL]) enzyme activities, anti-oxidant enzyme (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]) activities, malondialdehyde (MDA), lactate and glycogen contents, gill histological parameters (lamellar length [SLL], width [SLW], interlamellar distance [ID]), respiratory frequency (RF), the proportion of the secondary lamellae available for gas exchange (PAGE), and hifs (hif-1α, hif-2α, hif-3α) expression were determined during long-term hypoxia and reoxygenation. Results showed that long-term hypoxia (3.34 ± 0.17mg L-1) significantly elevated plasma cortisol and glucose contents; increased hepatic HK, PK, PFK, FAS, and LPL activity; decreased hepatic glycogen, lactate contents, and lipid drop numbers; and caused changes of hepatocyte (vacuolation, pyknotic, and lytic nucleus) after treatment for 4weeks. Hepatic SOD, CAT, GSH-Px activity, and MDA contents; lamellar perimeter, SLL, ID, RF, and PAGE; and hepatic hif-1α, hif-2α, and hif-3α manifested similar results. Meanwhile, hif-1α is significantly higher than hif-2α, and hif-3α. Interestingly, females and males demonstrated no sex dimorphism significantly different from the above parameters (except hepatic FAS, LPL activity, and lipid drop number) under hypoxia. The above parameters recovered to normal levels after reoxygenation treatment for 4weeks. Thus, long-term hypoxia promotes turbot hepatic glycogenolysis and lipolysis, induces oxidative damage and stimulates hepatic antioxidant capacity, and alters gill morphology to satisfy insufficient energy demand and alleviate potential damage, while hif-1α plays critical roles in the above physiological process.

Evaluating Lactate and D-Dimer as Mortality Predictors of Paediatric Multiple Organ Dysfunction Syndrome: A Prospective Study in a Low-Middle Income Country.

Multiple Organ Dysfunction Syndrome (MODS) is a complex medical condition characterised by dysfunction across multiple organs. With limited information available on mortality prediction in the paediatric population, particularly in low-middle income countries, this study evaluates the mortality predicting capabilities of lactate, D-dimer, and their combination. This prospective study involved paediatric patients admitted to the paediatric intensive care unit (PICU) of the largest central children's hospital in the Mekong Delta region, Vietnam, from 2019 to 2021. The discriminative ability and calibration of both individual and combined tests were assessed using the receiver operating characteristic (ROC) curves and the Hosmer-Lemeshow goodness-of-fit test. Among the patients studied, 63.1% did not survive. Lactate and D-dimer concentrations were significantly higher in the non-survivor group (P < 0.001). The area under the curve (AUC) values for lactate, D-dimer and the combined lactate-D-dimer test were 0.742, 0.775 and 0.804, respectively, with the combination showing the highest AUC value, though without statistical significance. Specific thresholds for lactate, D-dimer and the combination yielded sensitivities of 75.5%, 71.7%, and 66.0%, respectively. All three tests showed no statistically significant differences between observed and predicted mortality in the Hosmer-Lemeshow test (all P-values > 0.05). Lactate and D-dimer levels showed a significant association with mortality, along with good discrimination and calibration abilities. These results highlight the utility of lactate and D-dimer as effective predictors in paediatric MODS, particularly in resource-limited settings, and their role in improving patient outcomes.

An Integrated Approach Based on Clinical Data Combined with Metabolites and Biomarkers for the Assessment of Post-Operative Complications after Cardiac Surgery.

Background: Early diagnosis of post-operative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. The purpose of this study was to determine whether an integrated approach based on clinical data, along with metabolites and biomarkers, had greater predictive value than the models built on fewer data in the early diagnosis of post-operative complications after cardiac surgery. Methods: The study included patients (n = 62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass) with (n = 26) or without (n = 36) post-operative complications. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers and metabolites. Results: Multivariate PLS-DA models, predicting the presence or absence of post-operative complications, were built using clinical data, concentrations of metabolites and biomarkers, and the entire data set (ROC-AUC = 0.80, 0.71, and 0.85, respectively). For comparison, we built univariate models using the EuroScore2 and SOFA scales, concentrations of lactate, the dynamic changes of 4-hydroxyphenyllactic acid, and the sum of three sepsis-associated metabolites (ROC-AUC = 0.54, 0.79, 0.62, 0.58, and 0.70, respectively). Conclusions: The proposed complex model using the entire dataset had the best characteristics, which confirms the expediency of searching for new predictive models based on a variety of factors.

SUMO3 inhibition by butyric acid suppresses cell viability and glycolysis and promotes gemcitabine antitumor activity in pancreatic cancer

BackgroundExcavation of key molecules can help identify therapeutic targets and improve the prognosis of pancreatic cancer. This study evaluated the roles of SUMO3 in cell viability, glycolysis, gemcitabine (GEM) sensitivity, and the antitumor activity of butyric acid (BA) in pancreatic cancer.MethodsThe mRNA and protein levels of SUMO3 were detected by qRT-PCR, Western blot, and immunohistochemical assay. SUMO3 was silenced or overexpressed in pancreatic cancer cells with or without Wnt/β-catenin pathway inhibitor, glycolysis inhibitor, GEM, or BA treatment. Cell viability was measured using the Cell Counting Kit-8 assay. Glycolysis was measured by determining the extracellular acidification rate, ATP level, and lactate content. Apoptosis was measured by flow cytometry, and TUNEL staining was used to examine in vitro and in vivo sensitivity to GEM chemotherapy. Luciferase reporter and chromatin immunoprecipitation assays were conducted to detect the binding of the SUMO3 promoter and NF-κB p65.ResultsSUMO3 was increased and associated with poor survival in pancreatic cancer. SUMO3 knockdown decreased cell viability and glycolysis in vitro and inhibited tumor growth in vivo. SUMO3 overexpression increased cell viability and glycolysis in vitro through the β-catenin pathway. SUMO3 knockdown increased GEM sensitivity, whereas SUMO3 overexpression decreased GEM sensitivity and inhibited the antitumor activity of BA. BA promoted histone acetylation and p-IκBα expression to inhibit NF-κB p65-mediated SUMO3 transcription.ConclusionSUMO3 acted as an active molecule in cell survival and growth by enhancing glycolysis in response to either GEM or BA. The mechanism was related to the constitutive IκBα/NF-κB/SUMO3/β-catenin signaling pathway.

Social facilitation of trotting: Can horses perceive and adapt to the movement of another horse?

Exercise intensity is prone to be self-regulated in horses exercising freely. The main drivers include social, feeding and escape behaviors, as well as the operant conditioning. We hypothesized that self-regulated exercise intensity may increase due to the presence of another horse exercising ahead. Seven horses were assigned to a 2x2 crossover trial following treadmill familiarization. Video images of a trotting horse were displayed on the wall in front of the experimental unit (Visual), which was positioned in the treadmill. Physiological and behavioral markers were further compared with a control visual stimulus (Co), comprising a racetrack image without horses. Horses were sampled during a constant load exercise test (1) at rest (baseline), (2) after the warm-up (0 - 10th minute) and (3) after visual stimulation or control (10th- 12th minutes of the SET) to quantify plasma lactate and glucose concentration, heart rate, head angle, as well as behavioral markers. Following visual stimulation, heart rate (130.8 ± 27.8 b.p.m.) was higher than control (84.7 ± 15.1 b.p.m., P = .017), as was plasma lactate (Visual - 5.28 ± 1.48 mg/dl; Co -3.27 ± 1.24 mg/dl, P = .042) and head angle (Visual - 36.43 ± 3.69°; Co -25.14 ± 4.88°, P = .003). The prevalence of "ears forward" behavior was also higher following Visual (100% - 7/7) than Co (14% - 1/7, P = .004). These results suggest that visual stimulus (1) was safe and well tolerated and (2) prompted the anaerobic lactic pathways and shifted the behavior to a vigilant state. In conclusion, horses were able to perceive and adapt to a social environment. Our findings validate the use of social facilitation of trotting to encourage horses to move forward avoiding the use of the whip.

Intermittent hypoxic preconditioning reduces the risk of peri- and postoperative complications during on-pump cardiac surgery

Aim. To assess the effect of intermittent hypoxic-hyperoxic exposures (IHHE) on the outcomes of on-pump cardiac surgery.Material and methods. This prospective, single-center, randomized, controlled study was conducted in 110 patients with heart valve defects and/or aortic pathology from the cardiac surgery clinic of the I. M. Sechenov First Moscow State Medical University. The total sample was randomly divided into a group of patients who underwent IHHE (n=66) and a control group of patients who underwent placebo procedures with ambient air (n=44). The frequency and structure of intra-and postoperative complications were analyzed within 30 days after surgery. The presence of cognitive impairment, as well as serum troponin I and lactate concentrations were analyzed before and after surgery.Results. Peri- and early postoperative complications such as cardiac death, non-fatal infarction and acute heart failure occurred significantly less frequently in patients treated with IHHE compared with placebo group (1,6% vs 16,7%, p=0,009; 1,6% vs 16,7%, p=0,009; 6,3% vs 33,3%, p&lt;0,001, respectively). The median troponin I values 24 hours after surgery were 1,068 ng/ml (0,388-1,397 ng/ml) in the IHHE group and were significantly lower compared to the control group (1,980 ng/ml (1,068-3,239 ng/ml)). The serum lactate level after surgery was 1,8±0,7 mmol/l in the IHHE group and was significantly lower compared to the control group — 2,4±1,2 (p=0,05). Cognitive function, assessed by MOCA and MMSE tests, turned out to be significantly higher in patients who underwent a preoperative IHHE. No significant complications or serious adverse events were observed during the IHHE procedures.Conclusion. The use of individually adapted hypoxic preconditioning procedures reduces the incidence of peri- and postoperative complications, which is accompanied by a lower ischemia-reperfusion myocardial injury during artificial circulation with preservation of cognitive functions. IHHE procedures ramp up prehabilitation of patients referred for on-pump surgery of heart defects and aortic pathology.

Preparation and characterization of BSA-loaded liraglutide and platelet fragment nanoparticle delivery system for the treatment of diabetic atherosclerosis

BackgroundDiabetic atherosclerosis is one of the main causes of morbidity and mortality worldwide, but its therapeutic options are limited. Liraglutide (LIR), a synthetic analog of GLP-1 approved as an anti-obesity drug by the FDA, has been reported as a promising drug for diabetic atherosclerosis. However, the main problem with LIR is its use that requires regular parenteral injections, which necessitates the improvement of drug delivery for increased efficiency and minimization of injection numbers.ResultsThe objective of our present study was to prepare and characterize nanoparticles (BSA@LIR-PMF) for targeted drug delivery using LIR-encapsulated platelet membrane fragments (PMF) coated bovine serum albumin (BSA). We used various methods to characterize the prepared nanoparticles and evaluated their efficiency on diabetes-induced atherosclerosis in vitro and in vivo. The results showed that the nanoparticles were spherical and had good stability and uniform size with intact membrane protein structure. The loading and encapsulation rates (LR and ER) of BSA@LIR-PMF were respectively 7.96% and 85.56%, while the cumulative release rate was around 77.06% after 24 h. Besides, we also examined the impact of BSA@LIR-PMF on the proliferation, migration, phagocytosis, reactive oxygen species (ROS) levels, oxidative phosphorylation, glycolysis, lactate and ATP levels, and lipid deposition in the aortas. The results indicated that BSA@LIR-PMF could effectively inhibit ox-LDL-stimulated abnormal cell proliferation and migration, reduce the level of ROS and lactate concentration, and enhance the level of ATP, thereby improving oxidative phosphorylation in ox-LDL-treated cells.ConclusionBSA@LIR-PMF significantly inhibited diabetes-induced atherosclerosis. It was anticipated that the BSA@LIR-PMF nanoparticles might be used for treating diabetes-associated cardiovascular complications.

Dose-response effects of caffeine during repeated cycling sprints in normobaric hypoxia to exhaustion.

With limited studies exploring the dose-response of caffeine consumption on repeated sprint ability in hypoxia, this study aimed to determine the optimal caffeine dose (low, moderate or high) during repeated sprints in hypoxia to exhaustion. On separate visits, twelve active males randomly performed four experimental trials in normobaric hypoxia (inspired oxygen fraction: 16.5 ± 0.2%). Participants ingested placebo (PLA) or caffeine capsules (3, 6 or 9mg/kg or LOW, MOD and HIGH, respectively) 1h before exercise and then underwent a repeated cycling sprint test (10s sprint/20s active recovery) to exhaustion. Total sprint number and work done, peak and mean power output, blood lactate concentration, cardiorespiratory and perceptual responses were recorded. Total sprint number was greater in MOD and HIGH compared to PLA (20 ± 7 and 18 ± 8 vs. 13 ± 4; all P < 0.05), with MOD also higher than LOW (15 ± 6; P = 0.02). Total work done was greater in MOD (111 ± 40kJ) and HIGH (100 ± 35kJ) compared to LOW (83 ± 29kJ) and PLA (76 ± 25kJ) (all P < 0.05). However, there were no significant differences in total sprint number or total work done between MOD and HIGH (all P > 0.05). Blood lactate concentration was higher in both MOD and HIGH compared to PLA (all P < 0.05). However, peak and mean power outputs, fatigue index, and ratings of perceived exertion did not differ across different caffeine dosages (all P > 0.05). A moderate dose of caffeine (6mg/kg) is the optimal amount for enhancing repeated cycling sprint ability when compared to low and high doses in moderate normobaric hypoxia.

Insulin and leptin acutely modulate the energy metabolism of primary hypothalamic and cortical astrocytes.

Astrocytes constitute a heterogeneous cell population within the brain, contributing crucially to brain homeostasis and playing an important role in overall brain function. Their function and metabolism are not only regulated by local signals, for example, from nearby neurons, but also by long-range signals such as hormones. Thus, two prominent hormones primarily known for regulating the energy balance of the whole organism, insulin, and leptin, have been reported to also impact astrocytes within the brain. In this study, we investigated the acute regulation of astrocytic metabolism by these hormones in cultured astrocytes prepared from the mouse cortex and hypothalamus, a pivotal region in the context of nutritional regulation. Utilizing genetically encoded, fluorescent nanosensors, the cytosolic concentrations of glucose, lactate, and ATP, along with glycolytic rate and the NADH/NAD+ redox state were measured. Under basal conditions, differences between the two populations of astrocytes were observed for glucose and lactate concentrations as well as the glycolytic rate. Additionally, astrocytic metabolism responded to insulin and leptin in both brain regions, with some unique characteristics for each cell population. Finally, both hormones influenced how cells responded to elevated extracellular levels of potassium ions, a common indicator of neuronal activity. In summary, our study provides evidence that insulin and leptin acutely regulate astrocytic metabolism within minutes. Additionally, while astrocytes from the hypothalamus and cortex share similarities in their metabolism, they also exhibit distinct properties, further underscoring the growing recognition of astrocyte heterogeneity.

Determining lactate concentrations in Korean indigenous calves and evaluating its role as a predictor for acidemia in calf diarrhea

BackgroundCalf diarrhea leads to high mortality rates and decreases in growth and productivity, causing negative effects on the livestock industry. Lactate is closely associated with metabolic acidosis in diarrheic calves. However, there have been no reports on lactate concentrations in Korean indigenous (Hanwoo) calves, especially those with diarrhea. This study aimed to determine the reference range of L-lactate and D-lactate concentrations in Hanwoo calves and to better understand the utility of lactate as predictive factors for acidemia in diarrheic calves.ResultsL-lactate and D-lactate concentrations were measured in healthy (n = 44) and diarrheic (n = 93) calves, and blood gas analysis was performed on diarrheic calves. The reference range in healthy calves was 0.2–2.25 mmol/L for L-lactate and 0.42–1.38 mmol/L for D-lactate. Diarrheic calves had higher concentrations of L-lactate and D-lactate than healthy calves. In diarrheic calves, L-lactate and D-lactate each had weak negative correlation with pH (r = − 0.31 and r = − 0.35). In diarrheic calves with hyper-L-lactatemia, the combined concentrations of L-lactate and D-lactate had moderate correlation with pH (r = − 0.51) and anion gap (r = 0.55). Receiver operating characteristic analysis showed D-lactate had fair predictive performance (AUC = 0.74) for severe acidemia, with an optimal cut-off value of > 1.43 mmol/L. The combined concentrations of L-lactate and D-lactate showed fair predictive performance for predicting acidemia (AUC = 0.74) and severe acidemia (AUC = 0.72), with cut-off values of > 6.05 mmol/L and > 5.95 mmol/L.ConclusionsThe determined reference ranges for L-lactate and D-lactate in Hanwoo calves enable the identification of hyper-L-lactatemia and hyper-D-lactatemia. Diarrheic calves exhibited increased lactate concentrations correlated with acid-base parameters. While the concentrations of L-lactate and D-lactate have limitations as single diagnostic biomarkers for predicting acidemia or severe acidemia, their measurement remains important, and L-lactate has the advantage of being measurable at the point-of-care. Assessing lactate concentrations should be considered by clinicians, especially when used alongside other clinical indicators and diagnostic tests. This approach can improve calf diarrhea management, contributing positively to animal welfare and providing economic benefits to farms.

Comparison of lactate measurements from earlobe and fingertip capillary blood using Biosen S-Line and lactate scout analyzers.

This study aimed to compare variations between the earlobe and fingertip sampling sites in exercises dominated by upper body muscle exertion. It also sought to investigate capillary blood lactate differences between Lactate Scout 4 (LS4) and a bench-top analyzer (Biosen S-Line analyzer, BSL) during Double Poling. Blood samples were collected from the earlobe and fingertip immediately before exercise, at the end of each of five stages, and at 1-, 3-, 5-, and 7-min post-exercise. Forty healthy university students participated as volunteers. During the study, they performed double poling on a ski ergometer with progressively increasing load. Lactate levels were measured using both the BSL and LS4 analyzers. Fingertip Bla values were significantly higher than earlobe values, with a mean bias of -0.66mmol/L, reaching -0.86mmol/L in the 4-8mmol/L range. At the earlobe, the highest CCC between BSL and LS4-a was 0.84 (> 8mmol/L), and for BSL and LS4-b, it was 0.85 (> 8mmol/L). At the fingertip, the highest CCC between BSL and LS4-c was 0.68 (> 8mmol/L), and for BSL and LS4-d, it was 0.52 (> 8mmol/L). Comparing LS4-a and LS4-b at the earlobe, the highest CCC was 0.83 (0-4mmol/L). At the fingertip, comparing LS4-c and LS4-d, the highest CCC was 0.68 (> 8mmol/L). Blood lactate concentrations are higher at the fingertip than the earlobe during SkiErg double poling. The LS4 is less reliable, especially at the fingertip, so using the earlobe with the BSL analyzer is recommended for accurate measurements.

Effect of Low vs. High Carbohydrate Intake after Glycogen-Depleting Workout on Subsequent 1500 m Run Performance in High-Level Runners.

Carbohydrate (CHO) metabolism is crucial for short-duration, high-intensity exercise performance, but the effects of variations in glycogen availability have not been investigated in field trials of trained athletes. This study was designed to test how 1500 m time trial (TT) performance is affected by the manipulation of pre-race glycogen reserves. Competitive middle-distance runners (n = 11 (4 females)) completed a 1500 m individually paced indoor TT after abundant (high, >5 g/kg/d) or restricted (low, <1.5 g/kg/d) dietary CHO intake for 2 days after a glycogen-depleting session. Stride pattern, heart rate (HR), capillary blood lactate, and glucose and plasma malondialdehyde (MDA) response were determined. The TT was slower in low vs. high condition by 4.5 (4.5) s (~2%; p < 0.01), with a tendency toward shorter stride length. Blood lactate and glucose were lower before the TT in low vs. high condition (1.8 (0.5) vs. 2.2 (0.7) mmol/L and 5.4 (0.7) vs. 5.9 (0.8) mmol/L, p = 0.022 and 0.007, respectively), and peak lactate was higher in high vs. low condition (16.8 (3.1) vs. 14.5 (4.2) mmol/L, p = 0.039). Plasma MDA was the same before the TT, and 15 min after the TT, it increased similarly by 15% in low (p = 0.032) and high (p = 0.005) conditions. The restriction of pre-test CHO intake impaired 1500 m TT performance and reduced baseline and peak blood lactate concentrations but not blood glucose or MDA response.

Precision and accuracy of four handheld blood lactate analyzers across low to high exercise intensities.

To evaluate the precision and accuracy in measured blood lactate concentrations among four commonly used handheld lactate analyzers compared to two stationary analyzers. Venous blood samples were taken at exercise intensities ranging from low to high. The blood lactate concentration was measured simultaneously with four pairs of handheld lactate analyzers (two new units of each brand: Lactate Plus, Lactate Pro2, Lactate Scout 4, and TaiDoc TD-4289), and compared with two stationary analyzers (Biosen C-Line and YSI Sport 1500). Measurements were repeated for a range of blood lactate concentrations (measured with Biosen) from 0.88 to 4.89mM with a median difference between measurements of 0.10 mM. The mean relative differences to the Biosen analyzer were 7% (Plus), 7% (Pro), 10% (Scout), 42% (Tai), and 32% (Ysi). The residual standard errors after linear regression against Biosen were 0.18 mM (Plus), 0.20 mM (Pro), 0.22 mM (Scout), 0.15 mM (Tai), and 0.06 mM (Ysi). Accordingly, a blood lactate concentration of 3mM measured with Biosen yielded 95% prediction intervals that were 0.72 mM (Plus), 0.80 mM (Pro), 0.87 mM (Scout), 0.60 mM (Tai), and 0.23 mM (Ysi) wide. Compared to our two stationary analyzers, the precision of the four handheld lactate analyzers evaluated in this study was poor. Among the four, Tai was the most precise; however, this analyzer had low accuracy with a substantial mean difference to the reference analyzer.